The clue is in the brainstem

A 14-month-old female born to consanguineous parents with a history of gross motor delay was brought in with concerns that she was unable to move her eyes horizontally. Physical examination revealed a complete absence of horizontal eye movements with sparing vertical eye movements. The rest of the neurological examination was unremarkable. Magnetic resonance imaging (MRI) of the brain was performed [Figure 1] and showed characteristic brainstem deformities. The patient had a radiograph of the spine at the age of 21 months [Figure 2].Figure 1: (a and b) Axial T2-weighted images, (c) Sagittal T1-weighted image, and (d-f) Axial constructive interference in steady state imagesFigure 2: A radiograph with anteroposterior view of the chest and abdomenQuestions What is the deformity of the medulla called in this rare condition? A) Kinked medulla B) Butterfly medulla C) Double medulla D) Split medulla What is the primary genetic mutation causing such findings? A) ROBO3 B) C2CD3 C) ARL3 D) AH11 In addition to horizontal gaze palsy and characteristic MRI findings, what is the other salient finding of this disorder that Figure 2 is showing? A) Dextrocardia B) Spinal dysraphism C) Scoliosis D) Bronchiectasis. Answers B) A) C). Discussion MRI brain of the patient shows “butterfly shaped medulla” [Figure 1a]. There is also hypoplasia of the pons, tenting of the fourth ventricle, and the absence of facial colliculi [Figure 1b]. Sagittal T1-weighted image [Figure 1c] also shows the hypoplasia of the brainstem. In Figure 1d-f, axial constructive interference in the steady state (CISS) images demonstrates the butterfly appearance of the medulla with bilateral prominent inferior olivary nuclei [arrows in Figure 1d], confirm the presence of abducens nerves [arrows in Figure 1e], and show the midline cleft in the pons “split pons sign” [arrow in Figure 1f]. The MRI findings are consistent with horizontal gaze palsy with progressive scoliosis (HGPPS), which was confirmed with whole exome sequencing that revealed a homozygous pathogenic variant at ROBO3-gene at c.2770_2779+21del. Both parents were heterozygous for the same variant. The radiograph of the spine that was performed for the patient at the age of 21 months showed mild scoliosis [Figure 2]. HGPPS is a rare congenital autosomal recessive condition. It is characterized by complete horizontal gaze palsy along with the development of progressive severe scoliosis.[1] MRI brain findings are characteristic. Biallelic pathogenic variant(s) in ROBO3-gene have been found to cause this condition. The abnormality is thought to be in the medial longitudinal fasciculus (MLF) and not in the abducens nuclei. The evidence for this came from colored diffusion tensor imaging, where the tegmentum containing MLF was compromised due to the displacement of the corticospinal tracts.[2] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient’s parents have given their consent for the images and other clinical information to be reported in the journal. The parents understand that the patient’s name and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflict of interest There are no conflicts of interest.